The present invention is concerned with the use of starch containing amylose as a complexant with iodine for preparing dry powder pharmaceutical formulations useful in the preparation of capsules or tablets.
More particularly, the invention is concerned with the administration of molecular iodine (I.sub.2) to patients suffering from iodine deficiency diseases. Heretofore, I.sub.2 has been administered to patients in aqueous molecular form. The administration of aqueous molecular iodine to patients has several disadvantages including the need for specialized dispensers utilizing selective membranes thereby preventing the patient from ingesting crystallized iodine. Standardization of daily dosage is also a problem associated with these dispensers. See U.S. Pat. No. 4,384,960 to Polley.
In view of the apparent disadvantages to the administration of aqueous molecular iodine, it became evident that it would be desirable to administer the iodine in capsule or tablet form. The present invention is directed to dry pharmaceutical formulations containing iodine and the administration of the same in capsule or tablet form. This mode of administration of iodine is believed to be superior to those prior art methods and overcomes the various disadvantages experienced by the administration of elemental iodine in aqueous form.
In general, starch contains about 20 percent of a water-soluble fraction called amylose, and 80 percent of a water-insoluble fraction called amylopectin. These two fractions appear to correspond to different carbohydrates of high molecular weight and formula (C.sub.6 H.sub.10 O.sub.5).sub.n. Upon treatment of acid or under the influence of enzymes, the components of starch are hydrolized progressively to dextrin which is a mixture of low-molecular-weight polysaccharides, (+)-maltose, and finally D-(+)-glucose. Both amylose and amylopectin are made up of D-(+)-glucose units, but differ in molecular size and shape.
Of particular interest is the structure of amylose which is a linear 1,4-acetal polymer of glucose. Thus, amylose is made up of chains of many D-(+)-glucose units, each in and joined by an .alpha.-glycoside linkage to C-4 of the next glucose unit. It is the alpha linkage at the acetal carbon which has a profound effect on the overall shape of the giant amylose molecule which gives it its unique physical properties and the interactions the amylose molecule may have with smaller molecules.
Amylose is a helical molecule, with glucose residues that coil back on each other, creating a loosely overlapping spiral with a central cavity or tube.
A variety of small molecules including iodine, form weak complexes with amylose. As is known, the starch-iodine complex has a deep blue-violet colour that can be used to test for the presence of either amylose or iodine. From structural evidence, it is apparent that the colour arises because of interactions between rows of I.sub.3.sup.- molecules oriented end to end inside the tubular cavity of amylose structure (see Organic Chemistry, Kemp-Vellaccio, Worth Publishers, Inc., copyright 1980, p. 994).
It is the unique physical properties of the amylose molecule which forms a part of starch which has led us to believe that starch would be ideally suited as a complexant for iodine to prepare dry pharmaceutical formulations which may be encapsulated in capsule or pill form for oral administration. These dry formulations of iodine would be superior to known aqueous iodine solution used in the treatment of iodine deficiency diseases such as breast dysplasia, breast cancer, endometriosis and premenstrual syndrome. Such aqueous formulations are contemplated in U.S. Pat. No. 4,816,225 to Ghent et al issued Mar. 28, 1989, and WO90/07339, published Jul. 12, 1990. Dry powder formulations of the present form in capsule or tablet form are also useful in the treatment of radiation sickness from nuclear fallout and the like and are more easily administrable in oral form to patients. See for example U.S. Pat. No. 4,384,960 to Polley which discloses a dispenser of aqueous elemental iodine for oral administration to prevent or cure iodine-deficient goiter.